The ghrelin signalling system is involved in the consumption of sweets

The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose- intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours. © 2011 Landgren et al.

The role of near adaptation in myopia development

Prolonged near work is associated with myopia development in children and young adults but the reason underlying this association is unknown. Two potentially important factors are the near work induced ocular adaptations of contrast and accommodative adaptation. This study measured the degrees of contrast and accommodative adaptation during and following reading in myopic and emmetropic children and young adults in Singapore, where myopia is highly prevalent. Reading caused significantly greater contrast and accommodative adaptations in myopic children and myopic young adults compared to that measured in emmetropes of comparable ages. The adaptations were greater in magnitude in children than young adults, suggesting that children are more susceptible to ocular changes induced by reading and thus are potentially at greater risk of adverse refractive outcomes from these adaptations. In addition to the magnitude of the adaptations the regression time of these adaptations, (i.e. their durations) are also important. Longer accommodative adaptation regression times were measured for myopic children than for emmetropic children. Although the regression of contrast adaptation was not measured, its duration may likewise be important. The refractive effects of both of these adaptations are likely to be cumulative across the day and this could promote myopia in susceptible individuals performing considerable amounts of near work. Whether the type of text read affected the magnitude of the adaptations was also explored. Given the high prevalence of myopia in Chinese children and the fact that Chinese text is more complicated to write than English text, it was hypothesized that Chinese text would induce greater adaptation. However, both Chinese and English text produced similar amounts of accommodative and contrast adaptation in young adult subjects. We propose that children who spend prolonged periods reading at a young age are most vulnerable to near work induced adaptations and hence near work induced myopia. Both Chinese and English texts produce these effects and we propose that these adaptations are likely to occur for all types of common reading texts.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

Action research as foresight methodology

To the action researcher, who laboriously spends his or her hours working within the local contexts of communities or organisations to co-generate meaningful research, and who’s theories are hardened on the anvil of creating meaningful social change; futures studies might seem the discipline the most peripheral to its interests, and the most ill equipped to deal with the local and intimate domain of community existence. To the futurist, who laboriously spends his or her hours understanding the nuances of history and social change, who through persistent work, begins to make sense of the weak signals and the subtle shifts, action research would seem as simply an auxiliary field, inappropriate for understanding the greater scheme. I invite the reader, however, whether they belong to one camp or the other, to let go of their respective disciplinary perspectives, and see both belonging to each other. [Introduction] .

Investigation to enhance high speed rail accessibility

High Speed Rail (HSR) is rapidly gaining popularity worldwide as a safe and efficient transport option for long-distance travel. Designed to win market shares from air transport, HSR systems optimise their productivity between increasing speeds and station spacing to offer high quality service and gain ridership. Recent studies have investigated the effects that the deployment of HSR infrastructure has on spatial distribution and the economic development of cities and regions. Findings appear mostly positive at higher geographical scales, where HSR links connect major urban centres several hundred kilometres apart and already well positioned within a national or international context. Also, at the urban level, studies have shown regeneration and concentration effects around HSR station areas with positive returns on city’s image and economy. However, doubts persist on the effects of HSR at an intermediate scale, where the accessibility trade off on station spacing limits access to many small and medium agglomerations. Thereby, their ability to participate in the development opportunities facilitated by HSR infrastructure is significantly reduced. The locational advantages deriving from transport improvements appear contrasting especially in regions that tend to have a polycentric structure, where cities may present greater accessibility disparities between those served by HSR and those left behind. This thesis fits in this context where intermediate and regional cities do not directly enjoy the presence of an HSR station while having an existing or planned proximate HSR corridor. With the aim of understanding whether there might be a solution to this apparent incongruity, the research investigates strategies to integrate HSR accessibility at the regional level. While current literature recommends to commit with ancillary investments to the uplift of station areas and the renewal of feeder systems, I hypothesised the interoperability between the HSR and the conventional networks to explore the possibilities offered by mixed traffic and infrastructure sharing. Thus, I developed a methodology to quantify the exchange of benefits deriving from this synergistic interaction. In this way, it was possible to understand which level of service quality offered by alternative transit strategies best facilitates the distribution of accessibility benefits for areas far from actual HSR stations. Therefore, strategies were selected for their type of service capable of regional extensions and urban penetrations, while incorporating a combination of specific advantages (e.g. speed, sub-urbanity, capacity, frequency and automation) in order to emulate HSR quality with increasingly efficient services. The North-eastern Italian macro region was selected as case study to ground the research offering concurrently a peripheral polycentric metropolitan form, the presence of a planned HSR corridor with some portions of HSR infrastructure implementation, and the project to develop a suburban rail service extended regionally. Results show significant distributive potential, in terms of network effects produced in relation with HSR, in increasing proportions for all the strategies considered: a regional metro rail strategy (abbreviated RMR), a regional high speed rail strategy (abbreviated RHSR), a regional light rail transit (abbreviated LRT) strategy, and a non-stopping continuous railway system (abbreviated CRS) strategy. The provision of additional tools to value HSR infrastructure against its accessibility benefits and their regional distribution through alternative strategies beyond the actual HSR stations, would have great implications, both politically and technically, in moving towards new dimensions of HSR evaluation and development.

Diagnosed artist : what is the understanding of 'artist' held by a person with a mental illness?

What is the understanding of ‘artist’ held by a person with a mental illness? Being diagnosed with a mental illness often results in social isolation. Art programs are often used to address this isolation, and to expedite positive mental health and wellbeing. In these programs the cultural value of art can be moderated and replaced with therapeutic meanings or used for purposes of community integration. Some individuals develop artistic identities within these programs. These artists personify representative tensions within the art world. Artists with mental illness are symbolically positioned within the history of art as holding special creative providence and, yet are also viewed as having a peripheral position outside the cultural framework of the art world. This research engaged with eight artists to determine the understanding of artist held by a person with a mental illness. Through shared activities around the curatorial aspects of an exhibition entitled "Artist Citizen" the impact of illness, culture and alterity were examined. Overlapping approaches of Community Cultural Development and Participatory Action Research have been used. A perspective of alterity is given which was apparent in transformative processes of the research. This thesis shows that alterity and difference are both important social resources as well as positions of isolation and discrimination. Finally, conclusions are presented that indicated that a more nuanced understanding of alterity offers potential to discussions of the complex experiences of a person with a mental illness to negotiate subjective constructions of an identity for participation in broader political, social, health and cultural contexts.

Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions

Introduction—Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether peripheral blood viral load is a marker of KS burden (total number of KS lesions), KS progression (the rate of eruption of new KS lesions), or both is unclear. We investigated these relationships in persons with AIDS. Methods—Newly diagnosed patients with AIDS-related KS attending Mulago Hospital, in Kampala, Uganda, were assessed for KS burden and progression by questionnaire and medical examination. Venous blood samples were taken for HHV8 load measurements by PCR. Associations were examined with odds ratio (OR) and 95% confidence intervals (CI) from logistic regression models and with t-tests. Results—Among 74 patients (59% men), median age was 34.5 years (interquartile range [IQR], 28.5-41). HHV8 DNA was detected in 93% and quantified in 77% patients. Median virus load was 3.8 logs10/106 peripheral blood cells (IQR 3.4-5.0) and was higher in men than women (4.4 vs. 3.8 logs; p=0.04), in patients with faster (>20 lesions per year) than slower rate of KS lesion eruption (4.5 vs. 3.6 logs; p<0.001), and higher, but not significantly, among patients with more (>median [20] KS lesions) than fewer KS lesions (4.4 vs. 4.0 logs; p=0.16). HHV8 load was unrelated to CD4 lymphocyte count (p=0.23). Conclusions—We show significant association of HHV8 load in peripheral blood with rate of eruption of KS lesions, but not with total lesion count. Our results suggest that viral load increases concurrently with development of new KS lesions.

Kiss

In an age of mobile phones, Facebook, Twitter and online dating, interactions in mediated environments often outnumber face to face encounters. Kiss is an interactive light artwork by artists Priscilla Bracks & Gavin Sade. Kiss reacts to people standing in front of the artwork looking at each other - the moment before kissing. Without interaction the work generates a seductive, ambient, red lighting display, that creates the restful sense of staring into a fire. A fleeting response of white light – like sparks flying in the air – occurs the moment before two faces touch. These sparks are visible in peripheral vision, but fade when the kissing couple turns to look at the work. This moment - as two people look at each other - is a primal moment when two people recognise each other. Face to face encounters with another person are a privileged phenomenon in which the other person's presence and proximity are strongly felt. Kiss does not respond to every instance of a kiss or a look. Its recognition algorithms are fussy, selecting some faces and not others. As in life it’s difficult to tell why sparks fly with some people but not with others. For some this will be felt as a glitch. “This machine should be part of my social life!” But it does promote trial and error, asking viewers to be intimate in public and look at each other for longer than otherwise socially normal. 10 minutes continuous eye contact is said in most cases to arouse sexual feelings in both parties. But even if we don’t look that long, a short time may be all that is needed to explore the face of the person we are looking at. We see that they are human like us. We experience beauty, difference, discomfort, perhaps even nervous laughing, before turning to a more intimate moment of recognition.

Particle wave

“Particle Wave” is comprised of six lenticular panels hung in an even, horizontal sequence. Each panel alternates between two solid colour fields as you move past it. There are six colours in total, with each colour represented twice in the spectrum. From left to right, the panels move through yellow, orange, magenta, violet, blue, green and back to yellow. The work’s title refers to the two competing theories of light, which can be understood as either paradoxical or complementary. Like these theories, the experience of viewing the work catches us in a double bind. While we can orient ourselves to see solid colour fields one by one, we are never able to fully capture them all at once. In fact, it is only through our continual movement, and the subsequent transitioning of visible colours that we register the complete spectrum. Through this viewing experience, “Particle Wave” actively engages with our peripheral vision and the transitory nature of perception. It plays with the fundamental pleasures of colour and vision, and the uneasy seduction of being unable to grasp multiple phenomena simultaneously.

Making connections : creative industries networks in outer-suburban locations

The role of networks and their contribution to sustaining and developing creative industries is well documented (Wittel 2001; Kong 2005; Pratt 2007). This article argues that although networks operate across geographical boundaries, particularly through the use of communication technologies, the majority of studies have focussed on the ways in which networks operate in a) specific inner-urban metropolitan regions or b) specific industries. Such studies are informed by the geographical mindset of creative city proponents such as Florida (2002) and Landry (2000) in which inner-urban precincts are seen as the prime location for creative industries activity, business development and opportunity. But what of those creative industries situated beyond the inner city? Evidence in Australia suggests there is increasing creative industries activity beyond the inner city, in outer-suburban and ex-urban areas (Gibson & Brennan-Horley 2006). This article identifies characteristics of creative industries networks in outer-suburban locations in Melbourne and Brisbane. It argues that supporting and sustaining creative industries networks in these locations may require different strategies than those applied to inner-city networks. The article thus contributes to the growing understanding of the cultural economic geography of creative industries.

Making connections : creative industries networks in outer urban locations

The role of networks and their contribution to sustaining and developing creative industries is well documented (Wittel 2001, Kong 2005, Pratt, 2007). This article argues that although networks operate across geographical boundaries, particularly through the use of communication technologies, the majority of studies have focussed on the ways in which networks operate among creative industry workers located in a) specific inner-urban metropolitan regions or b) specific industries. Such studies are informed by the geographical mindset of creative city proponents such as Florida (2002) and Landry (2000) in which inner-urban precincts are seen as the prime location or ‘hub’ for creative industries activity, business development and opportunity. But what of those creative industries situated beyond the inner city? Evidence in Australia suggests that there is increasing creative industries activity beyond the inner city, in outer-suburban and ex-urban areas (Gibson and Brennan-Horley 2006). This article identifies features of networks operating two outer-suburban locations.

The cementogenic differentiation of periodontal ligament cells via the activation of Wnt/β-catenin signalling pathway by Li+ ions released from bioactive scaffolds

Lithium (Li) has been widely used as a long-term mood stabilizer in the treatment of bipolar and depressive disorders. Li+ ions are thought to enhance the remyelination of peripheral nerves and also stimulate the proliferation of neural progenitor cells and retinoblastoma cells via activation of the Wnt/β-catenin signalling pathway. Until now there have been no studies reporting the biological effects of released Li+ in bioactive scaffolds on cemetogenesis in periodontal tissue engineering applications. In this study, we incorporated parts of Li+ ions into the mesoporous bioactive glass (MBG) scaffolds and showed that this approach yielded scaffolds with a favourable composition, microstructure and mesopore properties for cell attachment, proliferation, and cementogenic differentiation of human periodontal ligament-derived cells (hPDLCs). We went on to investigate the biological effects of Li+ ions themselves on cell proliferation and cementogenic differentiation. The results showed that 5% Li+ ions incorporated into MBG scaffolds enhanced the proliferation and cementogenic differentiation of hPDLCs on scaffolds, most likely via activation of Wnt/β-catenin signalling pathway. Further study demonstrated that Li+ ions by themselves significantly enhanced the proliferation, differentiation and cementogenic gene expression of PDLCs. Our results indicate that incorporation of Li+ ions into bioactive scaffolds is a viable means of enhancing the Wnt canonical signalling pathway to stimulate cementogenic differentiation of PDLCs.

Implications of lipid biology for the pathogenesis of schizophrenia

Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

The effect of oral metformin on insulin sensitivity in insulin-resistant ponies

Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15. mg/kg bodyweight (BW), orally, twice-daily, for 21. days to the metformin-treated group. The control group received a placebo. A FSIGT was conducted before and after treatment. The Minimal Model of glucose and insulin dynamics rendered indices describing SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and the disposition index (DI). The body condition score (BCS), BW and cresty neck score (CNS) were also assessed. There was no significant change in SI, Sg, AIRg, DI, BW, BCS or CNS in response to metformin, or over time in the control group. There were no measurable benefits of metformin on SI, consistent with recent work showing that the bioavailability of metformin in horses is poor, and chronic dosing may not achieve therapeutic blood concentrations. Alternatively, metformin may only be effective in obese ponies losing weight or with hyperglycaemia.